Ipratropium Bromide/Levosalbutamol 1125 Ipratropium bromide may also be given by inhalation as a neb- 4. Bonadonna P, et al. Cold-induced rhinitis in skiers—clinical as- Profile ulised solution. UK licensed product information recommends pects and treatment with ipratropium bromide nasal spray: a ran- Isoetarine is a sympathomimetic with mainly beta-adrenergic ac- the following doses: domized controlled trial. Am J Rhinol 2001; 15: 297–301. tivity. It has actions similar to those of salbutamol (p.1131) but is 5. Kim KT, et al. Pediatric Atrovent Nasal Spray Study Group. Use • under 6 years, for the treatment of acute asthma only: 125 to of 0.06% ipratropium bromide nasal spray in children aged 2 to less selective for beta2 adrenoceptors. Isoetarine has been used as 250 micrograms, given no more often than every 6 hours up 5 years with rhinorrhea due to a common cold or allergies. Ann a bronchodilator in the management of reversible airways ob- to a total daily dose of 1 mg Allergy Asthma Immunol 2005; 94: 73–9. struction. • 6 to 12 years, for the treatment of acute or chronic asthma: Preparations Isoetarine is given by inhalation, as a nebulised solution of the 250 micrograms, repeated if necessary up to a total daily dose hydrochloride in strengths up to 0.25%; a 1% solution can be BP 2008: Ipratropium Nebuliser Solution; Ipratropium Powder for Inhala- given by a hand nebuliser. of 1 mg tion; Ipratropium Pressurised Inhalation. • 12 years and over: adult doses, see above. Proprietary Preparations (details are given in Part 3) Preparations Arg.: Aerotrop; Atrovent; Iprabron; Austral.: Aeron; Apoven; Atrovent; USP 31: Isoetharine Inhalation Solution; Isoetharine Mesylate Inhalation Ipratropium bromide is used in the management of rhinorrhoea Ipratrin; Ipravent; Austria: Atrovent; Itrop; Belg.: Atronase; Atrovent; Aerosol. associated with rhinitis. A dose of 42 micrograms may be given Braz.: Alvent†; Ares; Atrovent; Bromovent; Iprabon; Ipraneo; Canad.: into both nostrils two or three times daily. In the UK this dose Apo-Ipravent; Atrovent; Novo-Ipramide; Chile: Atrovent; Neorinol†; Cz.: may be given to children from 12 years of age, but in the USA Atrovent; Itrop†; Denm.: Atrovent; Fin.: Atrovent; Fr.: Atrovent; Ger.: this dose is licensed in children from 6 years of age. Atrovent; Itrop; Gr.: Atrovent; Hong Kong: Atrovent; Cyclovent; Levosalbutamol (rINN) ⊗ Ipravent†; Hung.: Atrovent; India: Ipranase; Ipravent; Indon.: Atrovent; US licensing also permits higher doses for up to 4 days when Irl.: Atrovent; Rinatec; Israel: Aerovent; Apovent; Atrovent; Ital.: Atem; Levalbuterol; Lévosalbutamol; Levosalbutamolum. (R)-α1-[(tert- rhinorrhoea is associated with the common cold: Rinovagos; Jpn: Atrovent; Malaysia: Atrovent; Mex.: Atrovent; Neth.: Butylamino)methyl]-4-hydroxy-m-xylene-α,α′-diol. Atrovent; Ipraxa; Norw.: Atrovent; Respontin†; NZ: Apo-Ipravent; Atrov- • 5 to 11 years: 84 micrograms into each nostril three times ent; Ipra†; Philipp.: Atrovent; Pol.: Atrovent; Port.: Atrovent; Rus.: Atro- Левосальбутамол daily vent (Атровент); S.Afr.: Atrovent; Ipvent; Singapore: Atrovent; Spain: C H NO = 239.3. Atrovent; Swed.: Atrovent; Switz.: Atrovent; Rhinovent; Thai.: Atrovent; 13 21 3 • 12 years and over: adult doses, see above Turk.: Atrovent; UAE: Atropulm; UK: Atrovent; Respontin; Rinatec; USA: CAS — 34391-04-3. Higher doses are also permitted in the USA for up to 3 weeks Atrovent; Venez.: Alovent. when rhinorrhoea is associated with seasonal allergic rhinitis. Multi-ingredient: Arg.: Berodual; Combivent; Ipradual; Iprasalb; Salbutral Children 5 years of age and over may be given the same dose as AC; Salbutrop†; Austral.: Combivent; Austria: Berodual; Berodualin; H OH Combivent; Di-Promal; Belg.: Combivent; Duovent; Braz.: Combivent; H adults, see above. Duovent; Canad.: Combivent; Duovent; ratio-Ipra Sal UDV; Chile: Berod- N CH3 ual; Combivent; Salbutral AC; Cz.: Berodual; Combivent†; Denm.: Berod- Asthma. Ipratropium bromide is currently recommended as an ual; Combivent; Fin.: Atrodual; Atrovent Comp; Fr.: Bronchodual; Combiv- adjunct to beta2 agonists in the management of acute severe asth- ent; Ger.: Berodual; Gr.: Berodual; Berovent; Hong Kong: Berodual†; H3C CH3 ma, see p.1108. Antimuscarinic drugs, mainly ipratropium but Combivent; Hung.: Berodual; India: Duolin; Fenovent; Indon.: Berodual; HO also including oxitropium (p.1129), glycopyrronium and atro- Combivent; Irl.: Combivent; Duovent; Ipramol; Ital.: Breva; Duovent; Ipraf- en; Malaysia: Berodual; Combivent; Duovent; Ipramol; Mex.: Berodual; pine, have been reviewed in the treatment of both acute and Combivent; Neth.: Berodual; Combivent; NZ: Combivent; Duolin; 1 OH chronic asthma. A systematic review and meta-analysis of the Philipp.: Berodual; Combipul; Combivent; Duavent; Pol.: Berodual; Port.: effectiveness of antimuscarinics in the treatment of acute asthma Berodual; Combivent; Rus.: Berodual (Беродуал); S.Afr.: Atrovent Beta; in children and adults, found they produced significant reduc- Berodual; Combivent; Duolin; Duovent; Sabax Combineb; Sabax Nebrafen; Singapore: Berodual; Combivent; Duovent; Spain: Berodual†; Combiv- Levosalbutamol Hydrochloride (rINNM) ⊗ tions in hospital admissions. Combined treatment with an in- ent; Legis†; Swed.: Combivent; Switz.: Berodual; Dospir; Thai.: Berodual; haled beta2 agonist also produced a significant increase in respi- Combivent; Inhalex; Punol; Turk.: Combivent; UK: Combivent; Duovent; Hidrocloruro de levosalbutamol; Levalbuterol Hydrochloride ratory function. Ipramol; USA: Combivent; DuoNeb; Venez.: Berodual; Combivent; Duo- (USAN); Lévosalbutamol, Chlorhydrate de; Levosalbutamoli Hy- lin; Duovent; Ipralin; Respidual. Systematic reviews of antimuscarinic drugs have concluded that drochloridum. (R)-α1-[(tert-Butylamino)methyl]-4-hydroxy-m- there is currently insufficient evidence to justify their routine use xylene-α,α′-diol hydrochloride. 2 3 in adults or children with chronic asthma. Левосальбутамола Гидрохлорид 1. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treat- Isoetarine (BAN, rINN) ⊗ C13H21NO3,HCl = 275.8. ment of children and adults with acute asthma: a systematic re- Isoetariini; Isoetarin; Isoetarina; Isoétarine; Isoetarinum; Iso- CAS — 50293-90-8. view with meta-analysis. Thorax 2005; 60: 740–6. etharine (USAN); Win-3406. 1-(3,4-Dihydroxyphenyl)-2-isopro- 2. Westby M, et al. Anticholinergic agents for chronic asthma in Pharmacopoeias. In US. adults. Available in The Cochrane Database of Systematic Re- pylaminobutan-1-ol. USP 31 (Levalbuterol Hydrochloride). A 1% solution has a pH views; Issue 3. Chichester: John Wiley; 2004 (accessed Изоэтарин of 4.5 to 5.5. Store in airtight containers at 20° to 25°, excursions 18/02/08). C H NO = 239.3. permitted between 15° and 30°. Protect from light. 3. McDonald NJ, et al. Anticholinergic therapy for chronic asthma 13 21 3 in children over 2 years of age. Available in The Cochrane Data- CAS — 530-08-5. base of Systematic Reviews; Issue 1. Chichester: John Wiley; ATC — R03AC07; R03CC06. Levosalbutamol Sulfate (rINNM) ⊗ 2003 (accessed 18/02/08). ATC Vet — QR03AC07; QR03CC06. Levalbuterol Sulfate (USAN); Lévosalbutamol, Sulfate de; Levos- Chronic obstructive pulmonary disease. Inhaled antimus- albutamol Sulphate; Levosalbutamoli Sulfas; Sulfato de levosalb- carinics, such as ipratropium bromide, are currently recommend- utamol. (R)-α1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene- OH ed as bronchodilators in chronic obstructive pulmonary disease αα′-diol sulfate (2:1). (COPD) guidelines, see p.1112. A systematic review compared Левосальбутамола Сульфат regular treatment with ipratropium (given for at least 4 weeks) CH3 with treatment using regular short-acting beta agonists in stable (C13H21NO3)2,H2SO4 = 576.7. 2 CAS — 148563-16-0. COPD;1 it found small benefits on lung function outcomes and HN CH3 quality of life with ipratropium compared with a short-acting HO beta agonist; a reduction in the requirements for oral corticoster- Levosalbutamol Tartrate (rINNM) ⊗ 2 OH CH3 oids was also seen. Combination therapy with ipratropium and a Levalbuterol Tartrate (USAN); Lévosalbutamol, Tartrate de; Lev- short-acting beta2 agonist was associated with some clinically o s a lb ut a m o li Ta r t r a s ; Ta r t r a t o d e l e vo s a l bu t am o l . ( α1R)-α1- meaningful lung function outcomes compared with the beta2 Isoetarine Hydrochloride (BANM, rINNM) ⊗ {[(1,1-Dimethylethyl)amino]methyl}-4-hydroxy-1,3-benzened- agonist alone, but these were not reflected in subjective improve- imethanol (2R,3R)-2,3-dihydroxybutanedioate (2:1). ments or symptom scores. Etyprenaline Hydrochloride; Hidrocloruro de isoetarina; Isoé- tarine, Chlorhydrate d’; Isoetarini Hydrochloridum; Isoetharine Левосальбутамола Тартрат A systematic review comparing ipratropium with a long-acting 2 Hydrochloride; N-Isopropylethylnoradrenaline Hydrochloride. 2(C13H21NO3),C4H6O6 = 628.7. beta2 agonist in stable COPD, found that salmeterol had more effect than ipratropium on lung function, but no major differenc- Изоэтарина Гидрохлорид CAS — 661464-94-4. es were seen between symptom responses to ipratropium and sal- C13H21NO3,HCl = 275.8. Adverse Effects and Precautions meterol. Combination treatment with these two drugs was better CAS — 50-96-4; 2576-92-3. As for Salbutamol, p.1131. than salmeterol alone in terms of quality of life. ATC — R03AC07; R03CC06. Incidence of adverse effects. Some studies have reported 1. Appleton S, et al. Ipratropium bromide versus short acting beta- ATC Vet — QR03AC07; QR03CC06. that beta-adrenergic adverse effects (e.g. nervousness and in- 2 agonists for stable chronic obstructive pulmonary disease. Pharmacopoeias. In US. creased heart rate) are less frequent with inhaled levosalbutamol Available in The Cochrane Database of Systematic Reviews; Is- 1-3 sue 2. Chichester: John Wiley; 2006 (accessed 18/02/08). USP 31 (Isoetharine Hydrochloride). A white to off-white, than with racemic salbutamol. Despite preliminary evidence 2. Appleton S, et al. Ipratropium bromide versus long-acting beta- odourless, crystalline solid. Soluble in water; sparingly soluble in that the increased airway hyperresponsiveness occasionally seen 2 agonists for stable chronic obstructive pulmonary disease. alcohol; practically insoluble in ether. A 1% solution in water has with long-term racemic salbutamol (see Tolerance, p.1132) may Available in The Cochrane Database of Systematic Reviews; Is- a pH of 4.0 to 5.6. Store in airtight containers. be due to the S(+)-enantiomer, and therefore might not occur sue 3. Chichester: John Wiley; 2006 (accessed 18/02/08). with levosalbutamol,4 a small study was unable to find any 5 Rhinitis. Ipratropium bromide is used intranasally for the treat- Isoetarine Mesilate (BANM, rINNM) ⊗ favourable protective effect. ment of rhinorrhoea in allergic and non-allergic rhinitis (p.565). 1. Nelson HS, et al. Improved bronchodilation with levalbuterol Isoétarine, Mésilate d’; Isoetarini Mesilas; Isoetharine Mesylate; compared with racemic albuterol in patients with asthma. J Al- It has also relieved rhinorrhoea and sneezing associated with the Isoetharine Methanesulphonate; N-Isopropylethylnoradrenaline lergy Clin Immunol 1998; 102: 943–52. common cold. Mesylate; Mesilato de isoetarina. 2. Milgrom H, et al. Low-dose levalbuterol in children with asth- References. ma: safety and efficacy in comparison with placebo and racemic Изоэтарина Мезилат albuterol. J Allergy Clin Immunol 2001; 108: 938–45. 1. Georgitis JW, et al. Ipratropium bromide nasal spray in non-al- C13H21NO3,CH4O3S = 335.4. 3. Handley DA, et al. Dose-response evaluation of levalbuterol lergic rhinitis: efficacy, nasal cytological response and patient versus racemic albuterol in patients with asthma. J Asthma 2000; evaluation on quality of life. Clin Exp Allergy 1994; 24: CAS — 7279-75-6. ATC — R03AC07; R03CC06. 37: 319–27. 1049–55. 4. Perrin-Fayolle M. Salbutamol in the treatment of asthma. Lancet 2. Hayden FG, et al. Effectiveness and safety of intranasal ipratro- ATC Vet — QR03AC07; QR03CC06. 1995; 346: 1101. pium bromide in common colds: a randomized, double-blind, Pharmacopoeias. In US. 5. Sjöswärd KN, et al. Single-isomer R-salbutamol is not superior placebo-controlled trial. Ann Intern Med 1996; 125: 89–97. USP 31 (Isoetharine Mesylate). White or practically white, to racemate regarding protection for bronchial hyperresponsive- 3. Dockhorn R, et al. Ipratropium bromide nasal spray 0.03% and ness. Respir Med 2004; 98: 990–9. beclomethasone nasal spray alone and in combination for the odourless, crystals. Freely soluble in water; soluble in alcohol; treatment of rhinorrhea in perennial rhinitis. Ann Allergy Asthma practically insoluble in acetone and in ether. A 1% solution in Interactions Immunol 1999; 82: 349–59. water has a pH of 4.5 to 5.5. Store in airtight containers. As for Salbutamol, p.1132. The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)